Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke

We will investigate the therapeutic efficacy of EEG-synchronized noninvasive repetitive transcranial magnetic stimulation (rTMS) in the early subacute phase after ischemic stroke to improve upper limb motor rehabilitation. We hypothesize that synchronization of rTMS with the phase of the ongoing sensorimotor oscillation indicating high corticospinal excitability leads to significantly stronger improvement of paretic upper limb motor function than the same rTMS protocol non-synchronized to the ongoing sensorimotor oscillation or sham stimulation.

Inclusion Criteria:Subjects meeting all of the following criteria will be considered for admission to the trial:Age ≥ 18 years at the time of signing the informed consent.Cerebral ischemia identified by brain imaging (cerebral MRI or CT) occurred 1-14 days ago.Subject understands and voluntarily signs an informed consent document prior to any study related assessments/procedures.Stroke has resulted in a new arm-/hand motor deficit with ≤ 50 points in the FMA-UE.Presence of motor evoked potentials (MEPs) in the paretic hand.If no MEPs can be obtained in the resting muscle, MEP search during isometric contraction of approx. 10-20% maximum voluntary contraction (MVC) in the target muscle is to be applied.If no MEPs can be obtained under contraction, MEP search with TMS double pulses (interstimulus interval (ISI) of 15 ms [41]) is to be applied.If still no MEPs can be obtained, TMS double pulses are to be applied during isometric contraction.If no MEPs can be obtained, MEP search procedure can be repeated later up to 14 days after stroke onset.μ-oscillation is recordable by EEG in the ipsilesional sensorimotor cortex as a 10 Hz peak with a sufficient signal-to-noise ratio of at least 3 dB.Subject is able to adhere to the study visit schedule and other protocol requirements.Exclusion Criteria:Subjects presenting with any of the following criteria will not be included in the trial:Hemorrhagic stroke (this refers to primary intracerebral hemorrhage only; hemorrhagic transformation of ischemic infarcts is not an exclusion criterion)Estimated life expectancy < 12 monthsPresence of intracranial ferromagnetic metal (extracranial stents ≥10 cm away from the TMS coil are acceptable) in accordance with current safety guidelines [18]Intraocular metal, cochlear implantsIf TMS might interact with sensors of active implants (e.g., intra-cardiac defibrillators).If a cranial bone gap affects currents induced by TMS (such as after craniotomy).History of seizures or epilepsy.Treatment intervention can't be started within 14 days after onset of stroke.Women during pregnancy and lactation.Participation in other clinical trials or observation period of competing trials.persistent addiction disorder (except for nicotine dependence)CNS malignomaIf there is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason the investigator considers the subject inappropriate for participation in the study.The ability to consent for patients who are unable to speak will be assessed on the basis of the NIHS-Score by an independent physician